Dietary nitrate increases submaximal SERCA activity and ADP-transfer to mitochondria in slow-twitch muscle of female mice
Journal article
Petrick, Heather, Brownell, Stuart, Vachon, Bayley, Brunetta, Henver, Handy, Rachel, Van Loon, Lucas, Murrant, Coral and Holloway, Graham. (2022). Dietary nitrate increases submaximal SERCA activity and ADP-transfer to mitochondria in slow-twitch muscle of female mice. American Journal of Physiology: Endocrinology and Metabolism. 323(2), pp. 1-14. https://doi.org/10.1152/ajpendo.00371.2021
Authors | Petrick, Heather, Brownell, Stuart, Vachon, Bayley, Brunetta, Henver, Handy, Rachel, Van Loon, Lucas, Murrant, Coral and Holloway, Graham |
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Abstract | Rapid oscillations in cytosolic calcium (Ca2+) coordinate muscle contraction, relaxation, and physical movement. Intriguingly, dietary nitrate decreases ATP cost of contraction, increases force production, and increases cytosolic Ca2+, which would seemingly necessitate a greater demand for sarcoplasmic reticulum Ca2+ ATPase (SERCA) to sequester Ca2+ within the sarcoplasmic reticulum (SR) during relaxation. As SERCA is highly regulated, we aimed to determine the effect of 7-day nitrate supplementation (1 mM via drinking water) on SERCA enzymatic properties and the functional interaction between SERCA and mitochondrial oxidative phosphorylation. In soleus, we report that dietary nitrate increased force production across all stimulation frequencies tested, and throughout a 25 min fatigue protocol. Mice supplemented with nitrate also displayed an ∼25% increase in submaximal SERCA activity and SERCA efficiency (P = 0.053) in the soleus. To examine a possible link between ATP consumption and production, we established a methodology coupling SERCA and mitochondria in permeabilized muscle fibers. The premise of this experiment is that the addition of Ca2+ in the presence of ATP generates ADP from SERCA to support mitochondrial respiration. Similar to submaximal SERCA activity, mitochondrial respiration supported by SERCA-derived ADP was increased by ∼20% following nitrate in red gastrocnemius. This effect was fully attenuated by the SERCA inhibitor cyclopiazonic acid and was not attributed to differences in mitochondrial oxidative capacity, ADP sensitivity, protein content, or reactive oxygen species emission. Overall, these findings suggest that improvements in submaximal SERCA kinetics may contribute to the effects of nitrate on force production during fatigue. |
Keywords | SERCA; calcium homeostasis; contractile function; mitochondria; nitrate |
Year | 01 Jan 2022 |
Journal | American Journal of Physiology: Endocrinology and Metabolism |
Journal citation | 323 (2), pp. 1-14 |
Publisher | American Physiological Society |
ISSN | 0193-1849 |
Digital Object Identifier (DOI) | https://doi.org/10.1152/ajpendo.00371.2021 |
PubMed ID | 35732003 |
Scopus EID | 2-s2.0-85135768820 |
Web address (URL) | https://journals.physiology.org/doi/full/10.1152/ajpendo.00371.2021 |
Open access | Published as green open access |
Research or scholarly | Research |
Page range | 1-14 |
Author's accepted manuscript | License All rights reserved File Access Level Open |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
01 Aug 2022 | |
Publication process dates | |
Accepted | 19 Jun 2022 |
Deposited | 05 Jan 2023 |
Additional information | Copyright © 2022 the American Physiological Society. |
Place of publication | United States |
https://acuresearchbank.acu.edu.au/item/8y905/dietary-nitrate-increases-submaximal-serca-activity-and-adp-transfer-to-mitochondria-in-slow-twitch-muscle-of-female-mice
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AM_Petrick_2022_Dietary_nitrate_increases_submaximal_SERCA_activity.pdf | |
License: All rights reserved | |
File access level: Open |
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